This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aging is characterized by a steady decline in an organism's ability to perform life-sustaining tasks. All organisms age, and this process is partially controlled by the regulation of gene expression. The lifespan of an organism is based on extrinsic factors, genes, and gene-environment interactions. Gene[unreadable]environment interactions are of considerable interest because they are especially relevant to aging in human populations that are not environmentally controlled. Little is known about the genetics of aging in most animals and even less is known in natural populations of species used as models for genetic research. For genetic analyses of aging, Drosophila melanogaster (fruit fly) is a useful model organism due to the genetic and genomic tools available, and ability to compare to humans because of the similarity in genes. Transcriptome studies have been conducted on D. melanogaster, but not in large populations that allow for many samples to be taken and for flies to be sampled at very old ages when all but a very small proportion of a cohort has died. The value of taking many samples is that temporal trends in gene expression become much clearer allowing for the identification of candidate genes that may be acting in a similar manner and, in fact, might allow for the identification of networks of gene expression. Replicate populations are valuable because they allow for identification of candidate genes whose pattern of expression is robust across populations. The main goal of the proposed research is to utilize use large laboratory populations of D. melanogaster recently derived from a natural population and thereby representing natural genetic variation to obtain comprehensive transcriptome profiles throughout the adult life span. The goals of this project are: 1) conduct a transcriptome analysis of large replicate populations recently derived from the field 2) validate the pattern of expression of candidate genes, 3) use mutations and P-element lines to test the effect of candidate genes. The overall goal of this research is to better understand the role of genes representing natural genetic variation throughout adult life including the very oldest ages, which is expected to provide unique insight into aging and longevity.